Micro-environment triple-responsive hyaluronic acid hydrogel dressings to promote antibacterial activity, collagen deposition, and angiogenesis for diabetic wound healing.

The clinical treatment of chronic diabetic wounds is a long-standing thorny issue. Strategies targeting the diabetic micro-environment have been developed to promote wound healing. However, it remains challenging to reverse the adverse conditions and re-activate tissue regeneration and angiogenesis. In this work, we develop injectable hydrogels that are responsive to acidic conditions, reactive oxygen species (ROS), and high glucose levels in a diabetic wound micro-environment to sustainably deliver tannic acid (TA) to augment antibacterial, anti-inflammatory, and anti-oxidative activities. This triple-responsive mechanism is designed by introducing dynamic acylhydrazone and phenylboronic ester bonds to crosslink modified hyaluronic acid (HA) chains. At a diabetic wound, the acylhydrazone bonds may be hydrolyzed at low pH. Meanwhile, glucose may compete with TA, and ROS may oxidize the C-B bond to release TA. Thus, sustained release of TA is triggered by the diabetic micro-environment. The released TA effectively scavenges ROS and kills bacteria. In vivo experiments on diabetic mice demonstrate that the hydrogel dressing highly promotes angiogenesis and extracellular matrix (ECM) deposition, leading to eventual full healing of diabetic skin wounds. This micro-environment-triggered triple-responsive drug release provides a promising method for chronic diabetic wound healing.

Gastrointestinal Fistulas in Necrotizing Pancreatitis Receiving a Step-Up Approach Incidence, Risk Factors, Outcomes and Treatment.

Purpose: Necrotizing pancreatitis (NP) complicated by gastrointestinal fistula is challenging and understudied. As the treatment of necrotizing pancreatitis changed to a step-up strategy, we attempted to evaluate the incidence, risk factors, clinical outcomes and treatment of gastrointestinal fistulas in patients receiving a step-up approach. Methods: Clinical data from 1274 patients with NP from 2014-2022 were retrospectively analyzed. Multivariable logistic regression analysis was conducted to identify risk factors and propensity score matching (PSM) to explore clinical outcomes in patients with gastrointestinal fistulas. Results: Gastrointestinal fistulas occurred in 8.01% (102/1274) of patients. Of these, 10 were gastric fistulas, 52 were duodenal fistulas, 14 were jejunal or ileal fistulas and 41 were colonic fistulas. Low albumin on admission (OR, 0.936), higher CTSI (OR, 1.143) and invasive intervention prior to diagnosis of gastrointestinal fistula (OR, 5.84) were independent risk factors for the occurrence of gastrointestinal fistula, and early enteral nutrition (OR, 0.191) was a protective factor. Patients who developed a gastrointestinal fistula were in a worse condition on admission and had a poorer clinical outcome (p<0.05). After PSM, both groups of patients had similar baseline information and clinical characteristics at admission. The development of gastrointestinal fistulas resulted in new-onset persistent organ failure, increased open surgery, prolonged parenteral nutrition and hospitalization, but not increased mortality. The majority of patients received only conservative treatment and minimally invasive interventions, with 7 patients (11.3%) receiving surgery for upper gastrointestinal fistulas and 11 patients (26.9%) for colonic fistulas. Conclusion: Gastrointestinal fistulas occurred in 8.01% of NP patients. Independent risk factors were low albumin, high CTSI and early intervention, while early enteral nutrition was a protective factor. After PSM, gastrointestinal fistulas resulted in an increased proportion of NP patients receiving open surgery and prolonged hospitalization. The majority of patients with gastrointestinal fistulas treated with step-up therapy could avoid surgery.

Timing of minimally invasive step-up intervention for symptomatic pancreatic necrotic fluid collections: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Minimally invasive step-up interventions are now the standard treatment recommended by current guidelines for symptomatic pancreatic necrotic fluid collections (PNFC); however, it is controversial whether delayed treatment after four weeks should always be used in patients who have failed conservative treatment and whose condition has not improved or worsened. The aim of this meta-analysis was to evaluate the impacts of the different timing of interventions on the clinical outcomes and prognosis of patients with symptomatic PNEC requiring intervention. METHODS: We searched Embase, Cochrane Library, PubMed and Web of Science databases to identify comparative studies assessing the safety and efficacy of early and postponed interventions in treating symptomatic PNFC. PRIMARY OUTCOME: Mortality. Secondary outcomes included some major complications, need for further minimally invasive necrosectomy and length of hospital stay. RESULTS: This meta-analysis included ten studies (2 RCTs and 8 observational studies) with a total of 1178 symptomatic PNFC patients who required intervention. Pooled results showed that there was no significant difference between early minimally invasive intervention and postponed intervention in mortality(OR 1.41, 95%CI 0.93-2.12;p = 0.10) and the incidence of early and late complications, but the early intervention group had a significantly increased need for further minimally invasive necrosectomy compared with postponed intervention (OR 2.04,95%CI 1.04-4.03; p = 0.04). There was no increase in length of stay for patients who received early intervention compared to postponed drainage (MD 3.53, 95% CI -4.20, 11.27; p = 0.37). CONCLUSION: Intervention before four weeks should be considered for patients with PNFC complicated by persistent organ failure or infections, who have been treated conservatively to the maximum extent possible.